The research addresses fundamental processes in the formation and survival of neurons, the impulse-conducting cells of the brain and nervous system. One goal is to determine how the decision of stem or precursor cells to become neurons through expression of proneural Class II bHLH genes relies on the earlier expression of genes that create a molecular environment either facilitating or antagonizing the future function of proneural Class II bHLH genes. Genetic and developmental studies of the fruitfly retina and the development of its photoreceptor neurons will be performed to delineate the regulatory network affecting proneural Class II bHLH genes. Molecular genetic studies will identify the specific DNA sequences that are responsible for gene expression and which therefore influence where and when neuronal photoreceptor cells are formed during eye development. A further goal is to determine how the genes that regulate neuronal determination also affect growth and the cell cycle. Genetic and molecular approaches will be taken to elucidate these connections between neurogenesis, growth, and cell cycle arrest, and which are perturbed in cancers and neurodegenerative diseases. PUBLIC HEALTH RELEVANCE: Neuronal deficits underlie common, serious health issues including retinitis pigmentosa, macular degeneration, stroke, Alzheimer's disease, Parkinson's Disease, Huntington's disease, and Amyotrophic Lateral Sclerosis. Replacing or limiting neuronal loss in these conditions would significantly improve or reverse symptoms. Our studies will suggest new approaches to neuroprotection and regenerative approaches involving proliferation and specification of replacement neurons.